The patterning of particles and cells, their positioning in specific locations on a substrate, is an increasingly important tool in a variety of applications, including the control of a cellular microenvironment. The cellular microenvironment is influenced by several factors—including cell-media, cell-matrix, and cell-cell interactions. Cell patterning can be used to manipulate cell-cell interactions, for example, by varying the contact area between two cell types in co-culture. Cell patterning can also be used to direct cell-matrix interactions, controlling the amount of contact area with the extracellular matrix (ECM) or the type of ECM upon which the cell is found.
Cell patterning has the potential to improve devices such as cell-based biosensors, the use of living cells as sensing elements for applications including toxin detection and defense monitoring. Cells have successfully been interfaced to sensing elements to form cell-based biosensors and recent advances in cell patterning may enable reproducible and readily manufactured biosensor devices, which would answer long felt needs for sensitive assays for biodefense application, for example.
Currently, there are a number of techniques for patterning cells. Microfluidic patterning takes advantage of the laminar flows in microfluidic devices to pattern the cell-culture substrate, cells, or cell-culture media. Other methods use physical barriers to position the cells, using for example, microwells or removable elastomeric stencils. Microcontact stamping of matrix proteins patterned onto a substrate and electroactive substrates with an applied voltage to switch the surface properties of the substrate, are both means used to facilitate selective cell attachment to specific regions of a substrate. Electromagnetic forces and optical tweezers have also been used to pattern cells.
To date, these techniques however, suffer limitations in their application in high-throughput settings, lack of resolution at a single cell level, produce unnatural and even traumatic effects on the manipulated cells, and lack the flexibility of manipulating the cells over time in an appropriate cellular milieu.